Preliminary studies suggest that the in vivo metastasis and growth patterns of lymphomas may be determined and/or predicted by their ability to interact with endothelial cells--particularly the specialized post-capillary, high endothelial venules (HEV) in lymphoid organs that mediate the exit of normal migrating lymphocytes from the blood. In the mouse, lymphomas that were unable to recognize and bind to HEV tended to grow primarily locally (e.g., as a local mass after subcutaneous injection), whereas HEV-binding lymphomas exhibited early symmetric involvement of all secondary lymphoid organs regardless of the route of injection. By using murine lymphomas as animal models, we will define rigorously the relationship between endothelial cell (HEV) recognition ability and the tendency of lymphomas for generalized spread to lymphoid organs. We will examine the relationship between (1)\the locale and kinetics of in vivo growth of lymphomas; (2)\their HEV binding capability assayed in vitro on frozen sections of lymph nodes or Peyer's patches; and (3)\their level of expression of a monoclonal antibody-defined lymphocyte surface protein ("receptor") which we have shown is involved in recognition of lymph node HEV. We will extend these studies to humans by (1)\adapting the in vitro frozen section assay to permit measurements of the binding of human lymphocytes, and (2)\attempting to produce monoclonal antibodies defining the human lymphocyte receptors for HEV. These assays or reagents will then be applied to the direct analysis of pathologic tissue specimens or cells, and the HEV receptor expression and recognition ability of human lymphomas and leukemias will be correlated with their histologic type and clinical behavior. These studies have the potential to identify an important functional and molecular correlate of the in vivo growth and spread of murine and human lymphomas and leukemias. They should provide us with ethical means of studying the migratory properties of normal and malignant lymphocytes in man; and they may yield monoclonal antibodies or a simple in vitro assay useful in predicting the metastatic potential of human lymphoid neoplasms.